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Gynecological Endocrinology : the... Dec 2024Premature ovarian insufficiency (POI) is a common gynecological endocrine disease, which seriously affects women's physical and mental health and fertility, and its... (Review)
Review
Premature ovarian insufficiency (POI) is a common gynecological endocrine disease, which seriously affects women's physical and mental health and fertility, and its incidence is increasing year by year. With the development of social economy and technology, psychological stressors such as anxiety and depression caused by social, life and environmental factors may be one of the risk factors for POI. We used PubMed to search peer-reviewed original English manuscripts published over the last 10 years to identify established and experimental studies on the relationship between various types of stress and decreased ovarian function. Oxidative stress, follicular atresia, and excessive activation of oocytes, caused by Stress-associated factors may be the main causes of ovarian function damage. This article reviews the relationship between psychological stressors and hypoovarian function and the possible early intervention measures in order to provide new ideas for future clinical treatment and intervention.
Topics: Humans; Primary Ovarian Insufficiency; Female; Stress, Psychological; Oxidative Stress; Risk Factors; Depression
PubMed: 38813955
DOI: 10.1080/09513590.2024.2360085 -
Gynecological Endocrinology : the... Dec 2024
Topics: Humans; Polycystic Ovary Syndrome; Female; Non-alcoholic Fatty Liver Disease; Adult; Risk Factors
PubMed: 38813954
DOI: 10.1080/09513590.2024.2359031 -
Turkish Journal of Medical Sciences 2023This study was designed to evaluate the relationship of two new biomarkers [tribbles homolog 3 (TRB3) and sestrin 2 levels], which were previously associated with...
BACKGROUND/AIM
This study was designed to evaluate the relationship of two new biomarkers [tribbles homolog 3 (TRB3) and sestrin 2 levels], which were previously associated with obesity, with metabolic parameters in obese and nonobese women with polycystic ovary syndrome (PCOS).
MATERIALS AND METHODS
This cross-sectional case control study was conducted between September 2017 and August 2019 in the gynecology department of a tertiary referral hospital. The values of the plasma sestrin 2, TRB3, insulin, fasting plasma glucose, lipid profile, and homeostasis model assessment of insulin resistance (HOMA-IR) were compared in 90 obese women with PCOS (BMI > 30), 90 women with nonobese PCOS (BMI < 30), and 90 control patients (BMI < 30).
RESULTS
The mean age of the study group consisting of all PCOS patients (26.11 ± 4.64 years) and the mean age of the control group (26.3 ± 4.4 years) were statistically similar (p = 0.239). The serum sestrin 2 values of the obese PCOS group were found to be statistically significantly lower than the control and non-obese PCOS groups (p = 0.001, p = 0.0001), while the sestrin 2 values of the nonobese PCOS group were found to be statistically significantly lower than the control group (p = 0.0001). The TRB3 values of the control group were found to be statistically significantly lower than the obese and nonobese PCOS groups (p = 0.0001), while the TRB3 values of the nonobese PCOS group were found to be statistically significantly lower than the obese PCOS group (p = 0.0001). A negative correlation was observed between the sestrin 2 level and BMI (r = -0.272 p = 0.0001), insulin (r = -0.261 p = 0.0001), and HOMA-IR levels (r = -0.250 p = 0.0001). A positive correlation was observed between the TRB3 values and TG (r = 0.248 p = 0.0001), and LDL-C values (r = 0.235 p = 0.0001).
CONCLUSION
According to the findings in this study, low sestrin 2 and high TRB3 levels may be related to impaired metabolic status in the obese PCOS group. Thus, it may be promising for the development of treatment of PCOS and associated metabolic disorder in the future.
Topics: Humans; Female; Polycystic Ovary Syndrome; Obesity; Adult; Case-Control Studies; Cross-Sectional Studies; Protein Serine-Threonine Kinases; Biomarkers; Insulin Resistance; Nuclear Proteins; Young Adult; Blood Glucose; Sestrins; Repressor Proteins; Cell Cycle Proteins
PubMed: 38813505
DOI: 10.55730/1300-0144.5738 -
Frontiers in Bioscience (Landmark... Apr 2024Ovarian cancer is a highly lethal gynecologic malignancy. ARHGAP10, a member of Rho GTPase-activating proteins, is a potential tumor suppressor in ovarian cancer....
BACKGROUND
Ovarian cancer is a highly lethal gynecologic malignancy. ARHGAP10, a member of Rho GTPase-activating proteins, is a potential tumor suppressor in ovarian cancer. However, its role and the involved mechanism need further examination. Here, we investigated whether ARHGAP10 is also associated with ferroptosis.
METHODS
Lentivirus infection was used for gene overexpression or silencing. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to assess mRNA and protein levels, respectively. Cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Lipid reactive oxygen species level was measured by flow cytometry. A tumorigenicity assay was performed to evaluate tumor growth , and sections of mouse tumor tissues were examined by immunofluorescence microscopy. Chromatin Immunoprecipitation (ChIP) assay was used to assess the binding of H3K9ac to the promoter region of ARHGAP10.
RESULTS
ARHGAP10 overexpression promoted ferroptosis in ovarian cancer cells, resulting in decreased cell viability, and increased lipid reactive oxygen species (ROS) level. Further, it decreased and increased GPX4 and PTGS2 expression, respectively, and also induced suppression of tumor growth in mice. Fer-1, a potent inhibitor of ferroptosis, suppressed the above effects of ARHGAP10. Contrarily, ARHGAP10 silencing alleviated ferroptosis in ovarian cancer cells, which was reversed by RSL3, a ferroptosis-inducing agent. Lastly, sodium butyrate (SB) was found to transcriptionally regulate ARHGAP10, thereby also contributing to the ferroptosis of ovarian cancer cells.
CONCLUSIONS
Our results suggest that SB/ARHGAP10/GPX4 is a new signaling axis involved in inducing ferroptosis in ovarian cancer cells and suppressing tumor growth, which has potential clinical significance.
Topics: Ferroptosis; Female; Ovarian Neoplasms; Humans; Animals; GTPase-Activating Proteins; Cell Line, Tumor; Reactive Oxygen Species; Butyric Acid; Gene Expression Regulation, Neoplastic; Mice; Mice, Nude; Cell Survival; Phospholipid Hydroperoxide Glutathione Peroxidase
PubMed: 38812318
DOI: 10.31083/j.fbl2905167 -
PloS One 2024Ovarian cancer is a challenging disease to diagnose and treat effectively with five-year survival rates below 50%. Previous patient experience research in high-income... (Observational Study)
Observational Study
The every woman study™ low- and middle-income countries edition protocol: A multi-country observational study to assess opportunities and challenges to improving survival and quality of life for women with ovarian cancer.
BACKGROUND
Ovarian cancer is a challenging disease to diagnose and treat effectively with five-year survival rates below 50%. Previous patient experience research in high-income countries highlighted common challenges and opportunities to improve survival and quality of life for women affected by ovarian cancer. However, no comparable data exist for low-and middle-income countries, where 70% of women with the disease live. This study aims to address this evidence gap.
METHODS
This is an observational multi-country study set in low- and middle-income countries. We aim to recruit over 2000 women diagnosed with ovarian cancer across multiple hospitals in 24 countries in Asia, Africa and South America. Country sample sizes have been calculated (n = 70-96 participants /country), taking account of varying national five-year disease prevalence rates. Women within five years of their diagnosis, who are in contact with participating hospitals, are invited to take part in the study. A questionnaire has been adapted from a tool previously used in high-income countries. It comprises 57 multiple choice and two open-ended questions designed to collect information on demographics, women's knowledge of ovarian cancer, route to diagnosis, access to treatments, surgery and genetic testing, support needs, the impact of the disease on women and their families, and their priorities for action. The questionnaire has been designed in English, translated into local languages and tested according to local ethics requirements. Questionnaires will be administered by a trained member of the clinical team.
CONCLUSION
This study will inform further research, advocacy, and action in low- and middle-income countries based on tailored approaches to the national, regional and global challenges and opportunities. In addition, participating countries can choose to repeat the study to track progress and the protocol can be adapted for other countries and other diseases.
Topics: Humans; Female; Ovarian Neoplasms; Quality of Life; Developing Countries; Surveys and Questionnaires; Asia; Africa; South America; Survival Rate; Adult; Middle Aged
PubMed: 38809901
DOI: 10.1371/journal.pone.0298154 -
Open Veterinary Journal Apr 2024Postpartum ovarian dysfunction [ovarian cyst (OC) and persistent follicle (PF)] has been an important issue. Finding effective hormonal treatments to improve...
BACKGROUND
Postpartum ovarian dysfunction [ovarian cyst (OC) and persistent follicle (PF)] has been an important issue. Finding effective hormonal treatments to improve reproductive performance in dairy cows has become a necessity.
AIM
Improve reproductive performance and ovarian activity in postpartum cows with specific customized treatment for OC and PFs.
METHODS
The study included 48 cows at 14 days P.P, which received two dosages of 500 μg IM cloprostenol, 14 days apart as presynchronization protocol. Ultrasound ovarian scans 14 days after the last injection for 4 weeks. The cows were divided into three groups according to ovarian status: OC ( = 14), PF ( = 12), and NE ( = 22). In the OC group, received 500 μg IM cloprostenol and 100 μg IM cystoriline, a second dose of cloprostenol 14 days later and a second dose of cystoriline 36 hours later, and AI after 24 hours (GnRH+ PG/PG/GnRH). In the PF group, was fitted with progesterone-releasing intravaginal device (PRID) for 9 days; the same day, they received 100 μg cystoreline then 500 μg cloprostenol 7 days later, after PRID removal AI 56 hours later (PRID + GnRH/PG). In the NE group, artificial insemination was implemented until 28 days depending on estrus detection.
RESULTS
The ovarian activity was greatly affected by the customized treatments, leading to enhanced follicular and luteal activity, particularly after the PGF2α injection. The OC and PF groups showed substantial estrus responses of 71.43% and 75.02%, respectively, during AI time. While the NE group had an ovulation rate of 54.5% and a pregnancy rate of 31.8%, the treatment groups showed marked improvements in reproductive performance. The ovulation rates in the OC and PF groups were 71.43% and 75% and the pregnancy rates at the 1st artificial insemination were 64.28% and 66.7%.
CONCLUSION
Improving reproductive performance and minimizing the time to first service are possible advantages of early case-specific treatment for postpartum cows with OC and PFs.
Topics: Animals; Female; Cattle; Ovarian Cysts; Postpartum Period; Cloprostenol; Cattle Diseases; Insemination, Artificial; Pregnancy; Ovarian Follicle; Progesterone; Estrus Synchronization
PubMed: 38808298
DOI: 10.5455/OVJ.2024.v14.i4.10 -
Clinical Case Reports Jun 2024Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder defined by the presence of at least two of the following conditions: chronic mucocutaneous...
KEY CLINICAL MESSAGE
Autoimmune polyglandular syndrome type 1 (APS-1) is a rare disorder defined by the presence of at least two of the following conditions: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism, and Addison's syndrome. Despite the lack of CMC and autoimmune history, APS-1 can be diagnosed using genetic testing.
UNLABELLED
We present the case of a 28-year-old female patient with a history of hypocalcemia due to hypoparathyroidism since the age of 2 years. She presented to the endocrine clinic with hypogonadism, primary amenorrhea, and primary ovarian insufficiency. Addison's disease was eventually diagnosed, despite a negative Synacthen test. The adrenal crisis required intravenous hydrocortisone therapy. No CMC was documented, and there was no family history of such conditions. The diagnosis of APS-1 was confirmed by genetic testing, revealing homozygous pathogenic variants of the autoimmune regulator gene. Management included oral calcium and calcitriol and oral hydrocortisone and fludrocortisone for Addison's disease. Hormonal induction of secondary sexual characteristics was initiated. The patient received combined oral estrogen and progesterone pills. This case highlights the critical significance of early recognition, thorough evaluation, and tailored treatment for patients with APS-1 to enhance their quality of life and mitigate potentially life-threatening complications. This underscores the importance of screening for associated minor autoimmune diseases as part of a holistic approach to care.
PubMed: 38808199
DOI: 10.1002/ccr3.9015 -
Oncology Letters Jul 2024The onset of two synchronous primary malignancies of the female genital tract is uncommon; therefore, the simultaneous occurrence of cervical small cell neuroendocrine...
The onset of two synchronous primary malignancies of the female genital tract is uncommon; therefore, the simultaneous occurrence of cervical small cell neuroendocrine carcinoma and ovarian immature teratoma is rare. The present study describes the case of a woman with cervical small cell neuroendocrine carcinoma complicated by ovarian immature teratoma. The clinical manifestations, and the histopathological and immunophenotypic features of the patient are recorded. Furthermore, all PubMed-indexed cases of synchronous primary malignancies in both the cervix and ovary have been briefly summarized.
PubMed: 38807671
DOI: 10.3892/ol.2024.14446 -
Journal of Experimental & Clinical... May 2024Ovarian cancer has a high mortality rate mainly due to its resistance to currently used therapies. This resistance has been associated with the presence of cancer stem...
BACKGROUND
Ovarian cancer has a high mortality rate mainly due to its resistance to currently used therapies. This resistance has been associated with the presence of cancer stem cells (CSCs), interactions with the microenvironment, and intratumoral heterogeneity. Therefore, the search for new therapeutic targets, particularly those targeting CSCs, is important for improving patient prognosis. HOOK1 has been found to be transcriptionally altered in a substantial percentage of ovarian tumors, but its role in tumor initiation and development is still not fully understood.
METHODS
The downregulation of HOOK1 was performed in ovarian cancer cell lines using CRISPR/Cas9 technology, followed by growth in vitro and in vivo assays. Subsequently, migration (Boyden chamber), cell death (Western-Blot and flow cytometry) and stemness properties (clonal heterogeneity analysis, tumorspheres assay and flow cytometry) of the downregulated cell lines were analysed. To gain insights into the specific mechanisms of action of HOOK1 in ovarian cancer, a proteomic analysis was performed, followed by Western-blot and cytotoxicity assays to confirm the results found within the mass spectrometry. Immunofluorescence staining, Western-blotting and flow cytometry were also employed to finish uncovering the role of HOOK1 in ovarian cancer.
RESULTS
In this study, we observed that reducing the levels of HOOK1 in ovarian cancer cells reduced in vitro growth and migration and prevented tumor formation in vivo. Furthermore, HOOK1 reduction led to a decrease in stem-like capabilities in these cells, which, however, did not seem related to the expression of genes traditionally associated with this phenotype. A proteome study, along with other analysis, showed that the downregulation of HOOK1 also induced an increase in endoplasmic reticulum stress levels in these cells. Finally, the decrease in stem-like properties observed in cells with downregulated HOOK1 could be explained by an increase in cell death in the CSC population within the culture due to endoplasmic reticulum stress by the unfolded protein response.
CONCLUSION
HOOK1 contributes to maintaining the tumorigenic and stemness properties of ovarian cancer cells by preserving protein homeostasis and could be considered an alternative therapeutic target, especially in combination with inducers of endoplasmic reticulum or proteotoxic stress such as proteasome inhibitors.
Topics: Female; Humans; Ovarian Neoplasms; Mice; Neoplastic Stem Cells; Animals; Autophagy; Cell Line, Tumor; Endoplasmic Reticulum Stress; Proteostasis; Microtubule-Associated Proteins; Cell Proliferation; Cell Movement
PubMed: 38807192
DOI: 10.1186/s13046-024-03071-2 -
BMC Medical Genomics May 2024Ovarian cancer is the most common cause of gynecological cancer death. Pak4 has been proved to be tumorigenic in many types of cancers, but its role in ovarian cancer is...
BACKGROUND
Ovarian cancer is the most common cause of gynecological cancer death. Pak4 has been proved to be tumorigenic in many types of cancers, but its role in ovarian cancer is still not clarified.
METHODS
In this study, we used immunohistochemistry to investigate into Pak4 expression in different histological types of ovarian cancer. TIMER, TISCH2, GEPIA, ualcan, KM plotter, GSCA and GeneMANIA were used to identify the prognostic roles and gene regulation networks of Pak4 in ovarian cancer. Immune infiltration levels were investigated using TIMER database.
RESULTS
Pak4 was highly expressed in ovarian cancers, regardless of different FIGO stages and histological grades. Single cell sequencing database proved that Pak4 was highly expressed in malignant ovarian cancer cells. Pak4 level was significantly correlated with different histological types of ovarian cancer. Pak4 expression was negatively connected with OS and PFS of ovarian cancer patients. Functions of Pak4 and its interacted genes were mainly involved in protein serine/threonine kinase activity, regulation of actin filament-based process and regulation of cytoskeleton organization. Pak4 level was negatively correlated with immune biomarkers of B cell infiltration (p = 2.39e-05), CD8 + T cell infiltration (p = 1.51e-04), neutrophil (p = 1.74e-06) and dendritic cell (p = 4.41e-08). Close correlation was found between Pak4 expression and T cell exhaustion (p < 0.05).
CONCLUSIONS
Our results demonstrated the expression level, gene interaction networks and immune infiltration levels of Pak4 in ovarian cancer. And the results revealed role of Pak4 in tumorigenesis and the possibility to be a potential immunotherapeutic target.
Topics: Humans; p21-Activated Kinases; Female; Ovarian Neoplasms; Gene Expression Regulation, Neoplastic; Prognosis; Carcinogenesis; Biomarkers, Tumor; Lymphocytes, Tumor-Infiltrating; Gene Regulatory Networks
PubMed: 38807162
DOI: 10.1186/s12920-024-01917-4